PUBLICATION
Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome
- Authors
- Cantagrel, V., Silhavy, J.L., Bielas, S.L., Swistun, D., Marsh, S.E., Bertrand, J.Y., Audollent, S., Attié-Bitach, T., Holden, K.R., Dobyns, W.B., Traver, D., Al-Gazali, L., Ali, B.R., Lindner, T.H., Caspary, T., Otto, E.A., Hildebrandt, F., Glass, I.A., Logan, C.V., Johnson, C.A., Bennett, C., Brancati, F.; International Joubert Syndrome Related Disorders Study Group, Valente, E.M., Woods, C.G., Gleeson, J.G.
- ID
- ZDB-PUB-080825-14
- Date
- 2008
- Source
- American journal of human genetics 83(2): 170-179 (Journal)
- Registered Authors
- Bertrand, Julien, Traver, David
- Keywords
- none
- MeSH Terms
-
- ADP-Ribosylation Factors/genetics*
- Abnormalities, Multiple/genetics
- Animals
- Brain Diseases/genetics*
- Chromosome Mapping
- Cilia/metabolism*
- Computational Biology
- Conserved Sequence
- Genetic Predisposition to Disease*
- Humans
- Molecular Sequence Data
- Mutation*
- Neurons/metabolism
- Syndrome
- Zebrafish
- PubMed
- 18674751 Full text @ Am. J. Hum. Genet.
Citation
Cantagrel, V., Silhavy, J.L., Bielas, S.L., Swistun, D., Marsh, S.E., Bertrand, J.Y., Audollent, S., Attié-Bitach, T., Holden, K.R., Dobyns, W.B., Traver, D., Al-Gazali, L., Ali, B.R., Lindner, T.H., Caspary, T., Otto, E.A., Hildebrandt, F., Glass, I.A., Logan, C.V., Johnson, C.A., Bennett, C., Brancati, F.; International Joubert Syndrome Related Disorders Study Group, Valente, E.M., Woods, C.G., Gleeson, J.G. (2008) Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome. American journal of human genetics. 83(2):170-179.
Abstract
Joubert syndrome (JS) and related disorders are a group of autosomal-recessive conditions sharing the "molar tooth sign" on axial brain MRI, together with cerebellar vermis hypoplasia, ataxia, and psychomotor delay. JS is suggested to be a disorder of cilia function and is part of a spectrum of disorders involving retinal, renal, digital, oral, hepatic, and cerebral organs. We identified mutations in ARL13B in two families with the classical form of JS. ARL13B belongs to the Ras GTPase family, and in other species is required for ciliogenesis, body axis formation, and renal function. The encoded Arl13b protein was expressed in developing murine cerebellum and localized to the cilia in primary neurons. Overexpression of human wild-type but not patient mutant ARL13B rescued the Arl13b scorpion zebrafish mutant. Thus, ARL13B has an evolutionarily conserved role mediating cilia function in multiple organs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping